National Human Genome Research Institute

National Institutes of Health U.S. Department of Health and Human Services

International HapMap Consortium Expands Mapping Effort

Map of Human Genetic Variation Will Speed Search for Disease Genes

BETHESDA, Md., Mon., Feb. 7, 2005 - The International HapMap Consortium,
boosted by an additional $3.3 million in public-private support, today announced
plans to create an even more powerful map of human genetic variation than originally
envisioned. The map will accelerate the discovery of genes related to common
diseases, such as asthma, cancer, diabetes and heart disease.

When the project was launched in October 2002, the consortium set September
2005 as the target for completing its map of common patterns of human genetic
variation, also known as haplotypes. By the end of February 2005, however, the
group already will have reached completion of its first draft of the human haplotype
map, or HapMap, which will consist of 1 million markers of genetic variation,
called single nucleotide polymorphisms (SNPs).

The consortium's new goal is to build an improved version of the HapMap that
is about five times denser than the original plan. This "Phase II"
HapMap will take advantage of the rapid, high-throughput genotyping capacity
of Perlegen Sciences, Inc., of Mountain View, Calif., to test another 4.6 million
SNPs from publicly available databases, and add that information to the map.
As a result of a grant competition last summer, Perlegen received a $6.1 million
award from the National Human Genome Research Institute (NHGRI), part of the
National Institutes of Health (NIH), to add data on 2.25 million additional
SNPs to HapMap. The new development, enabled by a partnership among multiple
funding sources, will expand that effort and test virtually the entire known
catalog of human variation on the HapMap samples. This will increase the density
of SNP "signposts" across the genome from the current average of one
every 3,000 bases to about one every 600 bases.

"This will help us create a far more powerful HapMap than we ever imagined.
We sincerely thank all those who are giving their time, technology and money
to help turn this dream into reality. The payoff will be a better understanding
of the genetic risk factors underlying a wide range of diseases and conditions,"
said NHGRI Director Francis S. Collins, M.D., Ph.D.

The first phase of the HapMap Project has allowed scientists to make important
analyses of the human genome that were not possible with just the human DNA
sequence, and the International HapMap Consortium plans to publish its comprehensive
analysis of this data later this year. The second phase of the project will
provide researchers with a denser map that will enable them to more precisely
narrow gene discovery to specific regions of the genome.

The effort to expand the HapMap is made possible by $3.3 million in additional
support from a unique public-private partnership, including the following organizations:
the Wellcome Trust, London, $624,000; Genome Canada/Genome Quebec, $260,000;
Bristol-Myers Squibb Co., New York, $100,000; Pfizer Inc., New York, $100,000;
Perlegen Sciences, at least $1.2 million (based on "in kind" services);
and NHGRI, $1 million. The donations from the two pharmaceutical companies were
coordinated by The SNP Consortium, Ltd., of Deerfield, Ill.

"Researchers are already using HapMap data to accelerate the search for
genes involved in common diseases, as well as genes involved in drug responsiveness,"
said Karen Kennedy, Ph.D., science program manager at the Wellcome Trust. "When
the more comprehensive version of the HapMap is completed this fall, such studies
will be able to be carried out with even greater speed and efficiency."

To create the HapMap, DNA was taken from blood samples from volunteer donors
from the following populations: Han Chinese in Beijing, Japanese in Tokyo, Yoruba
in Ibadan, Nigeria and Utah residents with ancestry from northern and western
Europe. No medical or personal identifying information was obtained from the
270 donors. However, the samples are identified by the population from which
they were collected.

Although any two people are 99.9 percent identical at the genetic level, understanding
the one-tenth of one percent difference is important because it helps explain
why one person may be more susceptible to a certain disease than another. For
any given disease, such as type II diabetes or coronary artery disease, researchers
can use the HapMap to compare the genetic variation patterns of a group of people
known to have the disease with a group of people without the disease. Finding
a certain pattern more often in people with the disease identifies a genomic
region that may contain genes contributing to the condition. Because the Phase
II HapMap will be so detailed, researchers will be able to use its SNP signposts
to zero in on that particular genomic region and search for specific genes involved
in that disorder. This approach can reduce the work and expense of searching
the genome for hereditary factors in common disease by a factor of 20 to 40
compared with current, brute force approaches.

"This new partnership underscores the private sector's enthusiasm for
the HapMap and its potential as a tool for the understanding of disease. The
willingness of these firms to contribute to building an even better map follows
the collaborative tradition established by The SNP Consortium," said Arthur
Holden, chairman and chief executive of The SNP Consortium.

In addition to affecting risk of disease, genetic variation has been shown
to affect the response of people to therapeutic drugs, toxic substances and
environmental factors, and the HapMap can assist in the identification of those
variants. Since not all genetic variants are deleterious, the HapMap also may
be used to help to pinpoint genetic variations that contribute to good health,
such as those protecting against infectious diseases or promoting longevity.

"We are excited by the opportunity to apply our technology to all publicly
available SNPs. This effort is so important that Perlegen is willing to contribute
some of its own resources to make this possible," said Kelly A. Frazer,
Ph.D., vice president of genomics at Perlegen. "We are confident that the
end result of this public-private collaboration will be an outstanding human
haplotype map that will provide a major new tool in the effort to combat human
disease through an understanding of its genetic components."

"Adding this large number of new SNPs to the map will make it even easier
for researchers to correlate genetic variation with gene function. Such information
is crucial for the development of therapies and preventive strategies tailored
to each person's unique genetic makeup," said Martin Godbout, Ph.D., president
and CEO of Genome Canada, who was also speaking on behalf of Genome Quebec.

The International HapMap Consortium is a public-private partnership of scientists
and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom
and the United States. The U.S. component of the $135 million international
project is led by NHGRI on behalf of the 19 institutes, centers and offices
of the NIH that contributed funding. For more information on the International
HapMap Project, see http://genome.gov/10001688 or http://hapmap.ncbi.nlm.nih.gov/. To
see a complete list of participating research organizations, see http://hapmap.ncbi.nlm.nih.gov/groups.html.

NHGRI is one of the 27 institutes and centers at the NIH, which is an agency
of the Department of Health and Human Services. The NHGRI Division of Extramural
Research supports grants for research and for training and career development
at sites nationwide. Additional information about NHGRI can be found at www.genome.gov.